TY - JOUR
T1 - Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model
AU - Wintjens, Anne G. W. E.
AU - Liu, Hong
AU - Fransen, Peter-Paul K. H.
AU - Lenaerts, Kaatje
AU - van Almen, Geert C.
AU - Gijbels, Marion J.
AU - Hadfoune, M'hamed
AU - Boonen, Bas T. C.
AU - Lieuwes, Natasja G.
AU - Biemans, Rianne
AU - Dubois, Ludwig J.
AU - Dankers, Patricia Y. W.
AU - de Hingh, Ignace H. J. T.
AU - Bouvy, Nicole D.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC.
AB - Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC.
KW - Peritoneal metastases model
KW - Colorectal cancer
KW - Intraperitoneal delivery
KW - Injectable supramolecular hydrogel
KW - Mitomycin C
KW - UPy-PEG
KW - HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY
KW - CYTOREDUCTIVE SURGERY
KW - SYSTEMIC CHEMOTHERAPY
KW - MITOMYCIN-C
KW - CARCINOMATOSIS
KW - CANCER
KW - PHARMACOKINETICS
KW - ORIGIN
KW - REGIMENS
KW - PATTERN
U2 - 10.1007/s10585-023-10210-0
DO - 10.1007/s10585-023-10210-0
M3 - Article
C2 - 37211565
SN - 0262-0898
VL - 40
SP - 243
EP - 253
JO - Clinical & Experimental Metastasis
JF - Clinical & Experimental Metastasis
IS - 3
ER -